Reductive Catalytic Difluorocarbene Transfer via Palladium Catalysis

A palladium-catalyzed reductive difluorocarbene transfer reaction that tames difluorocarbene to couple with two electrophiles has been developed, representing a new mode of difluorocarbene transfer reaction. The approach uses low-cost and bulk industrial chemical chlorodifluoromethane (ClCF2H) as the difluorocarbene precursor. It produces a variety of difluoromethylated (hetero)arenes from widely available aryl halides/triflates and proton sources, featuring high functional group tolerance and synthetic convenience without preparing organometallic reagents. Experimental mechanistic studies reveal that an unexpected Pd-0/II catalytic cycle is involved in this reductive reaction, wherein the oxidative addition of palladium(0) difluorocarbene ([Pd-0(L-n)]=CF2) with aryl electrophile to generate the key intermediate aryldifluoromethylpalladium [ArCF2Pd(L-n)X], followed by reaction with hydroquinone, is responsible for the reductive difluorocarbene transfer.